Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
Nanomedicine ; Humans ; Nanoparticles/chemistry* ; Pharmaceutical Preparations/chemistry* ; Animals ; Drug Carriers/chemistry*

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

The widespread abuse and high fatality rate of fentanyl and its analogs have posed a severe threat to global public health and safety.Metabolomics has emerged as a research hotspot in forensic science,as it enables the construction of in vivo models of drug toxicity mechanisms at the molecular level without direct drug detection,thereby elucidating metabolic pathways and evaluating toxic effects.Based on recent studies,this paper reviews commonly used strategies for metabolomics research and summarizes advances regarding endogenous biomarkers,metabolites,and toxicity mechanisms of fentanyl analogs,providing a reference for the application of metabolomics in the detection and control of these substances.

Objective Piperazine derivatives are a group of emerging psychoactive substances with excitatory and hallucinogenic effects on the central nervous system.This study established a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)screening method for the detection of 40 piperazine compounds in urine.Methods A 200 μL urine sample(spiked with an internal standard at 1 ng/mL)was subjected to liquid-liquid extraction with ethyl acetate.After nitrogen evaporation,the residue was redissolved in 200 μL methanol and injected for analysis.Separation was performed on a Waters Acquity UPLC? HSS T3 column(100 mm × 2.1 mm,1.8 μm).The mobile phase consisted of(A)20 mmol/L ammonium acetate buffer containing 0.1％formic acid and 5％acetonitrile,and(B)acetonitrile.Gradient elution was applied,and detection was carried out in multiple reaction monitoring(MRM)mode.Quantification was achieved using an internal standard calibration curve.Results The 40 piperazine substances demonstrated good linearity within the range of 1-50 ng/mL,with correlation coefficients of 0.995-0.998.The extraction recovery ranged from 51.51％to 104.1％.Intra-day precision was below 5％,while inter-day precision ranged from 1.61％to 10.17％.Accuracy was between-7.84％and 8.77％.The limits of detection were 0.2-1 ng/mL,and the limit of quantification was 1 ng/mL.Conclusion The proposed method requires only a small sample volume,exhibits high sensitivity,selectivity,and stability,and offers short run times.It is suitable for the qualitative and quantitative determination of piperazine derivatives in urine in forensic toxicology practice.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

The widespread abuse and high fatality rate of fentanyl and its analogs have posed a severe threat to global public health and safety.Metabolomics has emerged as a research hotspot in forensic science,as it enables the construction of in vivo models of drug toxicity mechanisms at the molecular level without direct drug detection,thereby elucidating metabolic pathways and evaluating toxic effects.Based on recent studies,this paper reviews commonly used strategies for metabolomics research and summarizes advances regarding endogenous biomarkers,metabolites,and toxicity mechanisms of fentanyl analogs,providing a reference for the application of metabolomics in the detection and control of these substances.

Objective Piperazine derivatives are a group of emerging psychoactive substances with excitatory and hallucinogenic effects on the central nervous system.This study established a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)screening method for the detection of 40 piperazine compounds in urine.Methods A 200 μL urine sample(spiked with an internal standard at 1 ng/mL)was subjected to liquid-liquid extraction with ethyl acetate.After nitrogen evaporation,the residue was redissolved in 200 μL methanol and injected for analysis.Separation was performed on a Waters Acquity UPLC? HSS T3 column(100 mm × 2.1 mm,1.8 μm).The mobile phase consisted of(A)20 mmol/L ammonium acetate buffer containing 0.1％formic acid and 5％acetonitrile,and(B)acetonitrile.Gradient elution was applied,and detection was carried out in multiple reaction monitoring(MRM)mode.Quantification was achieved using an internal standard calibration curve.Results The 40 piperazine substances demonstrated good linearity within the range of 1-50 ng/mL,with correlation coefficients of 0.995-0.998.The extraction recovery ranged from 51.51％to 104.1％.Intra-day precision was below 5％,while inter-day precision ranged from 1.61％to 10.17％.Accuracy was between-7.84％and 8.77％.The limits of detection were 0.2-1 ng/mL,and the limit of quantification was 1 ng/mL.Conclusion The proposed method requires only a small sample volume,exhibits high sensitivity,selectivity,and stability,and offers short run times.It is suitable for the qualitative and quantitative determination of piperazine derivatives in urine in forensic toxicology practice.

Hypertension heightens the risk of cardiovascular and renal complications in individuals with type 2 diabetes mellitus. Optimal blood pressure (BP) management is crucial for preventing these complications. This review consolidates evidence from clinical trials and major BP management guidelines to shed light on key aspects of hypertension management in diabetes. It addresses BP thresholds to initiate antihypertensive treatment, optimal BP control targets, recommended first-line antihypertensive edications, and BP monitoring plan for the prevention of chronic complications in type 2 diabetes.

Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

OBJECTIVE To screen the quality biomarkers of Gnaphalium affine with anti-chronic obstructive pulmonary disease （COPD） effect and determine their contents. METHODS The effective components and targets of “G. affine” with anti- COPD effect were predicted by using network pharmacology as a search criterion. HPLC fingerprints for 10 batches of G. affine were established by using Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）； common peak identification and similarity evaluation were conducted； cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed to screen differential components as quality maker that affected the quality of G. affine using variable importance projection （VIP）＞1 as the standard. The same HPLC method was adopted to determine the contents of the differential components in 10 batches of samples. RESULTS A total of 10 flavonoids （such as quercetin， luteolin， and chlorogenic acid） and organic acid components， were identified through network pharmacology search， with 91 targets closely related to anti-COPD. A total of 9 common peaks were identified in 10 batches of samples， with similarity greater than 0.90. Among them， the differential components included chlorogenic acid， caffeic acid， 1，3-O- dicaffeoylquinic acid and apigenin 7-O-β-D-glucopyranoside； S3， S4， S6， S7 and S10 were clustered into one category， S2， S5， S8 and S9 clustered into one category， and S1 clustered into one category. The contents of chlorogenic acid， caffeic acid， 1，3-O- dicaffeoylquinic acid， and apigenin 7-O-β-D-glucopyranoside in 10 batches of G. affine ranged 0.070-7.653， 0.010-0.097， 0.001- 0.036， 0.508-6.627 mg/g， respectively. CONCLUSIONS Chlorogenic acid， caffeic acid， 1，3-O-dicaffeoylquinic acid， apigenin 7- O-β-D-glucopyranoside can serve as the potential quality marker for the anti-COPD effect of G. affine， with the highest content of chlorogenic acid in G. affine produced in Ji’an， Jiangxi province， and the highest content of caffeic acid in G. affine produced in Ji’an， Jiangxi province and Sanming， Fujian province. The contents of the last two components are highest in G. affine produced in Chaoshan， Guangdong province.